The present invention concerns an apparatus for measuring the biomolecule interaction including a biosensor used in biochemical research, development of medicines, medical diagnosis, food inspection, etc.
In the existent measuring apparatus for biomolecules interaction, sensors utilizing a surface plasmon resonance method have been often used. The surface plasmon is compressive waves of free electrons propagating along the boundary between a metal thin film and a dielectric material and since this is greatly affected by the dielectric constant at the boundary, deposition of molecules to the surface can be detected by detecting the dielectric constant, which is used for the detection principle of immunosensors, gas sensors, etc.
However, since the surface plasmon resonance sensor has a complicate structure, Japanese Patent Laid-Open No. 2000-55920 proposes a sensor capable of measurement in a simple optical system as a fine noble metal sensor compared with the surface plasmon resonance sensor. A specific example of the fine noble metal sensor is described in Japanese Patent Laid-Open No. H11(1999)-1703. In this laid-open publication, fine particles such as of polymer, SiO2, TiO2, etc. is formed as a single layer on a noble metal thin film formed on a substrate, on which a noble metal such as gold, silver, copper, or platinum is vapor deposited or sputtered. This forms cap-shaped fine particles made of gold, silver, copper, platinum, etc. on fine particles. Another example of the fine noble metal particle sensor is described in Japanese patent Laid-Open No. H10(1998)-339808. This laid-open publication discloses that a substrate exhibits a remarkable color formation when fine noble metal particles are formed. The color formation is caused by absorption of a light for a portion of a wavelength region when a white light is reflected.
The absorption peak wavelength of the fine noble metal particles depends on the refraction index of the surface. Then, detection of the reaction that changes the refraction index of the surface is disclosed in Japanese Patent Laid-Open No. H11(1999)-326193. Further, Japanese Patent Laid-Open Nos. 2000-55920 and 2002-365210 describe that the surface can be modified by biomolecules having specific adsorption such as antibody and DNA, and utilized as a biosensor. Further, Japanese Patent Laid-Open No. 2002-228662 describes a biomolecule measuring apparatus at high sensitivity by utilizing fine noble metal particles.
In the measuring method of using the fine noble metal particle sensor described in each of the laid-open publications, fine noble metal particles modified by biomolecules are optically measured automatically. While the bonding of biobody molecules is measured as described above, no consideration has been taken for automatically depositing a liquid specimen or a buffer solution to fine metal particles. In a case where automatic optical measurement can be attained also including automatic deposition of the liquid specimen or the buffer solution to fine metal particles, a great amount of specimens can be treated in parallel by a small-sized apparatus in a short time.